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Biomedical subjects

M Peterson

Publications and source records attributed to M Peterson.

At least 37 records · Page 2Linked to original sources

Psychosocial and health-related characteristics of religious well-being.

This investigation examined the relationship between religions well-being and eight psychosocial and health-related characteristics. This study assessed the hypothesis that religious well-being is related to overall health. Participants were 462 college students at two separate colleges in the Pacific Northwest. Analysis showed those subjects scoring higher on the measure of religious well-being scored lower on indices like loneliness and hopelessness and higher on self-esteem. Alcohol and drug use also differed significantly between the high and the low, religious well-being groups.

Adolescent↗

Combined use of power Doppler and gray-scale sonography: a new technique for the assessment of inflammatory myopathy.

OBJECTIVE: Ultrasonography (US) is a utilitarian approach to the assessment of inflammatory myopathy (IM). Power Doppler sonography (PDS), a newer technique, enables detection of muscle vascularity and inflammation. We describe the combined use of PDS and gray-scale US in patients with IM. METHODS: We studied 37 IM subjects and 6 control subjects. Clinical scores of muscle strength and function were obtained. The maximum score, 31, represented normal function and strength. Ultrasonographic gray-scale and vascularity results were scored 0-4. Nine subjects had serial assessments. RESULTS: Subjects ranged from 16 to 83 years of age and were predominantly female. IM subjects had significantly abnormal lower clinical scores than controls, 23.0 +/- 5.8 vs 29.8 +/- 2.0 (p < 0.001). Mean peak gray-scale score was 2.1 +/- 0.96 compared to 0.5 +/- 0.84 for controls (p = 0.001), indicating atrophy in the IM group. Similar results were found for average gray-scale scores. Peak vascularity scores were higher in IM, 2.7 +/- 0.8 vs 2.2 +/- 0.3 (p = 0.007). Disease of longer duration was significantly associated with more abnormal gray-scale scores and lower creatine phosphokinase (CPK) levels. PDS scores were more abnormal in disease of shorter duration. There was a negative association between functional scores and inflammatory scores on serial assessment. CONCLUSION: Sonography is a valuable tool in the assessment of IM. Gray-scale and PDS findings were significantly different between IM and control subjects. Abnormal gray-scale US scores were associated with disease of longer duration and lower CPK levels. In contrast, increased vascularity on PDS detected disease of shorter duration and varied with the clinical course more than did gray-scale findings.

Adolescent↗

Estimated blood loss and transfusion requirements of radical cystectomy.

PURPOSE: Radical cystectomy has been associated with significant blood loss and/or transfusion requirement. We defined and characterized blood loss and transfusion parameters in this population. MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who underwent radical cystectomy and urinary diversion between October 1995 and July 2000. Charts were examined, and univariate and multivariate logistic regression analysis was performed to evaluate estimated blood loss and the transfusion requirement. RESULTS: Complete blood loss data were available in 297 cases. Overall 45% of patients had anemia preoperatively. Median estimated blood loss was 600 ml. (range 100 to 3,000). On univariate analysis increased estimated blood loss was related to patient age, American Society of Anesthesiologists score, longer operative time and paralytic ileus. Overall transfusion was done in 88 of 297 cases (30%) with a median requirement of 2 units (range 1 to 10). The transfusion rate in male and female patients was 26% and 40%, respectively (p <0.05). On univariate analysis female gender, ileal conduit diversion and lower preoperative hematocrit correlated with transfusion need (p = 0.04, <0.001 and <0.001, respectively). On multivariate logistic regression analysis lower preoperative hematocrit, increased estimated blood loss, major complications and ileal conduit diversion type correlated with a higher transfusion rate (odds ratio 8.34, 5.88 and 4.60, respectively). CONCLUSIONS: Acute blood loss anemia is common in patients undergoing radical cystectomy, and predicting blood loss and transfusion requirements remains difficult. These data indicate the need for continued refinement in surgical techniques to decrease blood loss as well as for strategies designed to decrease the need for blood transfusion.

Adult↗

Infection in total knee replacement: a retrospective review of 6489 total knee replacements.

Six thousand four hundred eighty-nine knee replacements were done in 6120 patients at the authors' institution between 1993 and 1999. Operations were done in a theater with vertical laminar flow and with the surgical team using body exhaust suits. Of these knee replacements, 116 knees became infected and 113 were available for followup. One hundred of the infections occurred in patients undergoing primary knee replacement, whereas the remaining infections occurred in patients undergoing revision knee replacement. Ninety-seven of these knees (86%) had deep periprosthetic infections and the remaining 16 knees had superficial wound infections. One third of the deep infections occurred within the first 3 months after surgery and the remaining 2/3 occurred after 3 months. The overall early deep infection rate for patients undergoing a primary knee replacement was 0.39%, whereas the rate for patients undergoing a revision knee replacement was 0.97%. A cohort of noninfected knee replacements from patients matched for gender, age, and month of surgery was used as a control group. Those comorbidities that were statistically significant in increasing the risk of infection were prior open surgical procedures, immunosuppressive therapy, poor nutrition, hypokalemia, diabetes mellitus, obesity, and a history of smoking. Patients undergoing revision procedures had a statistically higher risk of infection than did patients undergoing primary surgeries. If the surgery took longer than 2.5 hours, the risk of infection was increased significantly. There was no change in the infection rate when the perioperative antibiotic prophylaxis was decreased from 48 to 24 hours after surgery. The predominant infectious organisms were gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus Group B). Twenty percent of the knees that were infected clinically had no organisms that could be identified. In each case, the patient had been treated empirically at another institution with antibiotics before a culture of the joint was obtained.

Comorbidity↗

Pap smear screening in an equal-access health care system. Yield of screening and predictors of squamous intraepithelial lesions and atypical squamous cells of undetermined significance.

PURPOSE: The purpose of this study was to examine predictors of squamous intraepithelial lesions (SIL) and atypical squamous cells of undetermined significance (ASCUS) in an equal access health care setting.METHODS: A cohort of 10,713 active-duty United States Air Force women who provided one cervical/vaginal smear (CVS) as part of routine medical care between January 1, 1994 and December 31, 1996 were selected for this study. Each of the specimens was characterized by a "Bethesda System" diagnosis: within normal limits, repair/reactive, ASCUS, low grade SIL, high grade SIL, invasive carcinoma, infectious disease or unsatisfactory.RESULTS: Significant disease was associated with age younger than 30 years, enlisted rank, Hispanic ethnicity and the presence of genital warts on examination. SIL was associated with age 21-25 and Hispanic ethnicity in the logistic regression model. A diagnosis of ASCUS was associated with age younger than 30, marital status as single/never married, presence of genital warts on physical examination, and a history of previous abnormal CVS since entering military service. Age younger than 30, a marital status of single/never married and a previous abnormal CVS were associated with ASCUS in the logistic regression model.CONCLUSIONS: The disparity noted between women of low and high socioeconomic status was not seen here; those with the lowest income and education were not significantly more likely to have SIL or ASCUS when age was considered in the model. The significant association between Hispanic ethnicity and SIL, which should be further explored, may indicate the need for increased screening in this population.

Journal Article↗

The MHC class II molecule I-Ag7 exists in alternate conformations that are peptide dependent.

Insulin-dependent diabetes mellitus is an autoimmune disease that is genetically linked to the HLA class II molecule DQ in humans and to MHC I-Ag7 in nonobese diabetic mice. The I-Ag7 beta-chain is unique and contains multiple polymorphisms, at least one of which is shared with DQ alleles linked to insulin-dependent diabetes mellitus. This polymorphism occurs at position 57 in the beta-chain, in which aspartic acid is mutated to a serine, a change that results in the loss of an interchain salt bridge between alphaArg76 and betaAsp57 at the periphery of the peptide binding groove. Using mAbs we have identified alternative conformations of I-Ag7 class II molecules. By using an invariant chain construct with various peptides engineered into the class II-associated invariant chain peptide (CLIP) region we have found that formation of these conformations is dependent on the peptide occupying the binding groove. Blocking studies with these Abs indicate that these conformations are present at the cell surface and are capable of interactions with TCRs that result in T cell activation.

Animals↗

Translational control of the antiapoptotic function of Ras.

Activated Ras has been shown to provide powerful antiapoptotic signals to cells through well defined transcriptional and post- translational pathways, whereas translational control as a mechanism of Ras survival signaling remains unexplored. Here we show a direct relationship between assembly of the cap-dependent translation initiation apparatus and suppression of apoptosis by oncogenic Ras in vitro and in vivo. Decreasing protein synthesis with rapamycin, which is known to inhibit cap-dependent translation, increases the susceptibility of Ras-transformed fibroblasts to cytostatic drug-induced apoptosis. In contrast, suppressing global protein synthesis with equipotent concentrations of cycloheximide actually prevents apoptosis. Enforced expression of the cap-dependent translational repressor, the eukaryotic translation initiation factor (eIF) 4E-binding protein (4E-BPI), sensitizes fibroblasts to apoptosis in a manner strictly dependent on its ability to sequester eIF4E from a translationally active complex with eIF4GI and the co-expression of oncogenic Ras. Ectopic expression of 4E-BP1 also promotes apoptosis of Ras-transformed cells injected into immunodeficient mice and markedly diminishes their tumorigenicity. These results establish that eIF4E-dependent protein synthesis is essential for survival of fibroblasts bearing oncogenic Ras and support the concept that activation of cap-dependent translation by extracellular ligands or intrinsic survival signaling molecules suppresses apoptosis, whereas synthesis of proteins mediating apoptosis can occur independently of the cap.

Adaptor Proteins, Signal Transducing↗

Cryosolvents useful for protein and enzyme studies below -100 degrees C.

For the study of protein structure, dynamics, and function, at very low temperatures it is desirable to use cryosolvents that resist phase separation and crystallisation. We have examined these properties in a variety of cryosolvents. Using visual and X-ray diffraction criteria, methanol:ethanediol (70%:10%), methanol:glycerol (70%:10%), acetone:methoxy-ethanol:ethanediol (35%:35%:10%), dimethylformamide:ethanediol (70%:10%), dimethylformamide (80%), methoxyethanol (80%), and methoxyethanol:ethanediol (70%:10%) were all found to be free of phase-changes down to at least -160 degrees C. The least viscous of these, methanol:ethanediol (70%:10%), was miscible down to -125 degrees C and showed no exo or endothermic transitions when examined using DSC. It is therefore potentially particularly suitable for very low temperature cryoenzymology.

Cryoprotective Agents↗

Inhibition of Myc-dependent apoptosis by eukaryotic translation initiation factor 4E requires cyclin D1.

Ectopically expressed eukaryotic translation initiation factor 4E (eIF4E) stimulates cell proliferation, suppresses apoptosis in growth factor restricted cells, and induces malignant transformation in primary rodent fibroblasts when coexpressed with protooncogene myc. We report here that eIF4E rescued rat embryo fibroblasts ectopically expressing c-Myc (REF/Myc) from genotoxic and non-genotoxic cytostatic drugs and identify cyclin D1 as a downstream effector in the antiapoptotic mechanism. In clones of REF/Myc ectopically expressing eIF4E, resistance to apoptosis paralleled steady state levels of cyclin D1. Stable expression of cyclin D1 in REF/Myc inhibited apoptosis in response to a broad range of cell cycle specific cytostatic agents. Partial loss-of-cyclin D1 function in REF/Myc ectopically expressing eIF4E (REF/Myc/4E) significantly increased chemosensitivity; either soluble antisense cyclin D1 oligomers or transfection with a dominant negative cyclin D1 mutant that prevents translocation of cyclin D-dependent kinases to the nucleus, significantly blunted the antiapoptotic effect of eIF4E. These data directly link eIF4E rescue from cytostatic drugs to cyclin D1. Since overexpression of eIF4E and cyclin D1 is observed in many aggressive forms of chemoresistant cancers, these findings provide insight into possible mechanisms responsible for this biological behavior.

Animals↗

A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (Macaca fascicularis).

Ovariectomized cynomolgus monkeys have previously been investigated as a nonhuman primate model of postmenopausal osteoporosis (Jerome et al., Bone Miner 9:527-540; 1994). In the present study, Fourier transform infrared microspectroscopy (FTIRM) was used to verify that differences in bone mineral quality and quantity in the vertebrae of mature intact (INT) and ovariectomized (ovx) monkeys were analogous to those seen in osteoporotic and nondiseased human bones. FTIRM spectra were acquired from 15 trabeculae per vertebra from three ovx and three INT adult monkeys (mean age 8 years). These spectra were compared with those of both trabecular and previously reported osteonal bone obtained from 3 "normal" and 11 postmenopausal osteoporotic human subjects. While variations in the mineral:matrix ratio (mineral content), carbonate:phosphate ratio, and crystallinity are typical for trabecular bone from iliac crests of normal human subjects, the values of these parameters were relatively static for trabecular bone from postmenopausal osteoporotic human subjects. In general, trabecular bone from postmenopausal osteoporotic human subjects exhibited decreased mineral content (1.0 +/- 0.5 vs. 2.9 +/- 0.6), increased crystallinity, and increased carbonate:phosphate relative to controls. Similarly, trabecular bone from ovariectomized monkeys exhibited lower mineral content (5.8 +/- 0.2) compared with the INT group (6.2 +/- 0.2; p </= 0.05) and contained larger/more perfect apatite crystals (increased crystallinity) with increased carbonate:phosphate ratios. Variations in absolute values were attributable to site differences (ilium vs. vertebrae). To appreciate the importance of mineral properties on mechanical properties, compression testing was performed using cores of monkey L-3 and L-4 vertebral bodies from a separate group of monkeys. Treating monkeys with the anabolic steroid nandrolone decanoate (ND) immediately after ovariectomy and for the next 24 months (ND group), or beginning 12 months after ovariectomy (dND group), increased the ultimate stress compared with an ovx treatment group, despite large interanimal variations in bone architecture and mechanical properties. These data support the hypothesis that ovariectomized adult monkeys are an excellent model for postmenopausal osteoporosis, and can be used for the evaluation of therapeutic modalities.

Animals↗

Homogenous expression of killer cell immunoglobulin-like receptors (KIR) on polyclonal natural killer cells detected by a monoclonal antibody to KIR2D.

The activity of human natural killer (NK) cells is in part regulated by the expression of killer cell immunoglobulin (Ig)-like receptors (KIR) that recognize major histocompatibility complex (MHC) class I and can inhibit NK cell cytotoxicity. A monoclonal anti-KIR antibody was established and designated Lig1. Lig1 was shown to be specific for KIR in cell-surface staining and to react with all KIR2D, except KIR2DL4 which lacks a D1 domain, but not with KIR3D molecules in an enzyme-linked immunoadsorbent assay (ELISA) and Western blotting. Unlike other anti-KIR antibodies, Lig1 did not inhibit binding of KIR-Ig-fusion proteins to MHC-class I expressing cells nor did it interfere with KIR-mediated inhibition of NK cell cytotoxicity in a functional assay. Lig1 reacted with all NK cells in polyclonal NK populations from different donors, demonstrating that all NK cells express at least one KIR2D receptor.

Amino Acid Sequence↗

Marimastat inhibits neointimal thickening in a model of human arterial intimal hyperplasia.

OBJECTIVE: matrix metalloproteases (MMPs) produced by vascular smooth-muscle cells (VSMCs) degrade extracellular matrix and facilitate the migration of these cells. This is a fundamental process in arterial intimal hyperplasia. This study investigated whether Marimastat (a selective but non-specific MMP inhibitor) can prevent intimal hyperplasia in cultured human internal mammary artery (IMA). MATERIALS AND METHODS: segments of IMA from 8 patients were prepared and cultured for 14 days in serum-supplemented medium (control) or in medium supplemented with Marimastat at 2 concentrations (treatment groups). The tissue was fixed, sectioned, stained and neointimal thicknesses measured by computer-aided image analysis. Further sections were cultured in the same manner and prepared for gel enzymography to quantify the production of MMPs. RESULTS: neointimal thickness was significantly reduced by Marimastat in a dose-dependent manner when compared to controls (p =0.008 Wilcoxon). Gel enzymography demonstrated a reduction in levels of MMP2 and MMP9. This was most significant for the active forms of the enzymes ( p =0.03). CONCLUSIONS: our results suggest that there is a potential therapeutic role for specific inhibition of the gelatinases in the prevention of human arterial restenosis.

Cells, Cultured↗

Pneumatic compression hemodynamics in total hip arthroplasty.

A crossover study was performed to evaluate the effect of several pneumatic compression devices and active dorsoplantar flexion in 10 patients who underwent total hip arthroplasty. Using the Acuson 128XP/10 duplex ultrasound unit with a 5-MHz linear array probe, peak venous velocity and venous volume were assessed above and below the greater saphenous vein and common femoral vein junction. A computer generated randomization table was used to determine the order of the test conditions. The pneumatic compression devices evaluated included two foot pumps, one foot and calf pump, one calf pump, and three calf and thigh pumps. Statistical analyses included analysis of variance and analysis of variance with covariance between devices and patients. The covariates tested were the baseline measurements and the order in which the devices were tested. Differences between devices relate in part to the frequency and rate of inflation and the location and type of compression. Pulsatile calf and foot and calf pneumatic compression with a rapid inflation time produced the greatest increase in peak venous velocity, whereas compression of the calf and thigh showed the greatest increase in venous volume. Because patient and nursing compliance is essential to the success of mechanical prophylaxis for thromboembolic disease, the more simple, yet efficacious, devices that are easier to apply and less cumbersome appear to have a greater likelihood of success. In the active and alert patient, active dorsoplantar flexion should be encouraged.

Arthroplasty, Replacement, Hip↗

Increased cervical dysplasia in intravenous cyclophosphamide-treated patients with SLE: a preliminary study.

To determine if intravenous cyclophosphamide (IV-C) causes an excess of cervical dysplasia and/or cancer in systemic lupus erythematosus (SLE) patients, a retrospective review was conducted. Patients with SLE who received IV-C between 1988-98 (study group) were compared with a group of SLE patients who had not received IV-C (control group). Of the 79 IV-C-treated SLE patients identified, we excluded 18 because of absence of pertinent data. We found 10 cases of cervical dysplasia in the remaining 61 patients, compared to 2 in 49 non-exposed patients (P<0.04). Comparison of the two groups revealed no difference in: mean years of disease duration, months of follow-up and age. The non-exposed patients were more likely to be on estrogen and hydroxychloroquine but less often on steroids and azathioprine. The study group with and without dysplasia were assessed; we found no difference in the mean, or total IV-C dose, smoking and estrogen use. There was a significant decrease in time to dysplasia in those, given IV-C, with previous dysplasia compared to those without. These preliminary data suggests that IV-C causes an increased number of abnormal Papanicolaou (Pap) smears in SLE patients, particularly those with previous dysplasia.

Adult↗

Meta-analysis of thromboembolic prophylaxis after total knee arthroplasty.

We performed a meta-analysis of the English literature to assess the efficacy of four common regimes for thromboembolic prophylaxis after total knee arthroplasty: aspirin, warfarin, low-molecular-weight heparin (LMWH) and pneumatic compression. We reviewed 136 articles and abstracts published between January 1980 and December 1997. Papers not using routine venography and a lung scan or angiography to detect deep-venous thrombosis (DVT) and pulmonary emboli (PE) respectively, were excluded. Of the 136 studies, 23 with 6,001 patients were selected. The incidence of DVT was 53% (1,701/3,214) in the aspirin group, 45% (541/1,203) in the warfarin group, 29% (311/1,075) in the LMWH group, and 17% (86/509) in the pneumatic compression device group. Intermittent pneumatic compression devices and LMWH were significantly better than warfarin (p < 0.0001) or aspirin (p < 0.0001) in preventing DVT. The incidence of asymptomatic PE was 11.7% in the aspirin group (222/1,901), 8.2% (101/1,229) in the warfarin group and 6.3% (24/378) in the pneumatic compression group. No studies with LMWH used routine lung scans. Warfarin and pneumatic compression were significantly better than aspirin in preventing asymptomatic PE (p < 0.05). The incidence of symptomatic PE was 1.3% (23/1,800) in the aspirin group, 0.4% (2/559) in the warfarin group, 0.5% (2/416) in the LMWH group and 0% (0/177) in the pneumatic compression group. No statistically significant difference was noted between the above prophylactic regimes due to the very small incidence of symptomatic PE. Prophylaxis for thromboembolic disease in TKA may have to include a combination of some of the above regimes to incorporate their advantages.

Anticoagulants↗

Automatic and voluntary control of attention in young and older adults.

Young and older adults searched for a target character in a 3-item display. On each trial, both a symbolic cue (arrow at fixation) and a spatial cue (abrupt onset of one item) could indicate the target's position. Participants were told to use the central arrow cue on all trials because it had 75% validity. The onset cue also had 75% validity for half the participants and 25% validity for the other half. Both age groups showed about the same cost and benefit effects for the central arrow cues, but the abrupt onsets had much larger cuing effects for older adults. Young adults were able to suppress at least partially an automatic attentional response to an abrupt onset item when the arrow cue preceded the onset and had a higher validity than the onset cue. Older adults appeared to be less able to inhibit their responses to abrupt onsets and to disengage their attention from invalid onset cues than were the young adults.

Adult↗

Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. RESULTS: Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. CONCLUSIONS: Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.

Adult↗